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To describe epidemiological and clinical features of patients confirmed as having SARS-CoV-2 infection and managed in isolation at home. We performed a multicenter retrospective study enrolling all SARS-CoV-2-positive adults evaluated from 28 February to 31 May 2020 at one of nine COVID-19 Units in southern Italy: we included patients receiving care at home and those admitted to hospital. We defined patients with not-severe disease if they were asymptomatic or experienced a mild infection that did not need oxygen (O2) therapy and those with a severe infection if hospitalized and required O2 therapy. We enrolled 415 patients with SARS-CoV-2 infection: 77 were managed in isolation at home, 338 required hospital management. The 77 patients in home isolation were less frequently male than hospitalized patients (55% vs. 64%; <0.01) and were younger (median age 45 years (IQR:19) vs. 62 (IQR 22); p < 0.01), had a lower Charlson comorbidity index (median 0 (IQR2) vs. 6 (IQR 3); p < 0.01), and included fewer subjects with an underlying chronic disease (36% vs. 59%; p < 0.01). According to a binomial logistic regression analysis, a younger age (OR: 0.96 (95% IC: 0.94–0.98), p < 0.01) and a low Charlson comorbidity index (OR: 0.66 (95% IC: 0.54–0.83); p < 0.01) were independent factors associated with at-home management. The identification of subjects with SARS-CoV-2 infection who could be managed in home isolation is useful in clinical practice. A younger age and no comorbidities were identified as factors independently associated with home management.

Gallbladder volvulus in children is rare. Pre-operative diagnosis is considered difficult because of the nonspecific symptoms and inflammatory blood analysis findings. Sometimes diagnosis is confirmed at laparotomy. Many reports mention that the chief complaints of this disease are sudden and severe abdominal pain. We report a case of gallbladder volvulus in a boy with mild clinical symptoms and laboratory data of nonspecific inflammation. A reconstructed coronal CT abdominal view showed clearly the gallbladder torsion. Laparoscopic cholecystectomy was performed and postoperative course was uneventful. Recent reports have suggested the effectiveness of MRI. This case highlights the utility of a reconstructed coronal view of abdominal CT in successful pre-operative diagnosis for gallbladder volvulus in children.

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IntroductionKleine-Levin Syndrome (KLS) is an extremely rare disorder of unknown etiology. It affects mainly male adolescents and is thought to follow a relapse-remitting course. During episodes of illness, a wide array of neuropsychiatric symptoms may present and a psychiatric diagnosis might be incorrectly made.ObjectivesWe aim to review the literature on the clinical manifestations of KLS, as well as the current evidence regarding this disorder’s management.MethodsWe performed an updated review in the PubMed database using the terms “Kleine-Levin Syndrome”. The included articles were selected by title and abstract.ResultsKLS usually presents with recurrent episodes, lasting days to weeks, of severe hypersomnia, cognitive impairment, major apathy and derealization, among other neuropsychiatric symptoms. Although it was previously thought that complete normalization occurred between episodes, recent evidence suggests that around one third of patients have mild cognitive impairment and there are alterations in brain blood flow during the asymptomatic periods. During episodes of illness, management comprises environmental measures as well as drug therapy. Corticosteroids and amantadine have been successful in stopping episodes and lithium may be useful in a preventative role, however, there are no randomized controlled trials focusing on KLS treatment.ConclusionsKLS remains an elusive entity since it is an extremely rare disorder with unclear etiology, course, and no consensual treatment. Further research is warranted in this area, namely randomized controlled trials. It is important for the practicing psychiatrist to be aware of this illness in order to recognize it and adequately manage it.

Presenilin-1 (PSEN1) mutations predispose individuals to develop autosomal-dominant Alzheimer's disease (ADAD) in middle adulthood. While the pathogenesis of ADAD may be different from late-onset sporadic AD (e.g., differences in disease etiology, age of disease onset, etc), these conditions share many characteristics, including similar abnormalities in amyloid and tau biomarkers, brain structure and brain activity, and clinical features (Quiroz et al., 2010, Quiroz et al., 2011, Quiroz et al. 2018). Biomarker investigations of families with ADAD have already shed light on the trajectory of some AD-related brain changes, especially prior to the onset of clinical symptoms. We have been studying a Colombian kindred with a genetic form of AD caused by a single genetic mutation in the PSEN1 (E280A), which serves as a unique model for preclinical AD. Because of a well-defined age at clinical onset, and near 100% penetrance, this kindred provides important information about the time course and relationships between physiological mechanisms and cognitive changes, and in so doing, it has yielded new insights about presymptomatic AD that will enhance future prevention trials for AD, including primary prevention trials. The well-characterized clinical trajectory of these PSEN1 E280A mutation carriers allow us to examine brain function in children, more than three decades before the average age of onset of mild cognitive impairment (MCI) and dementia in this cohort (45 years for MCI, 50 years for dementia). This is giving us the unique opportunity to characterize the cognitive and behavioral profiles of children genetically determined to develop dementia in their forties, and is helping us improve our understanding of the impact of ADAD mutations in early life cognitive and brain functioning, as well as its potential impact on learning, academic performance and educational attainment. We previously studied 20 PSEN1 E280A carriers and 20 non-carriers aged 9 to 17 years from the Colombian ADAD cohort and showed that mutation-carrying children were distinguished from non-carriers by plasma biomarker findings consistent with Aß1-42 overproduction, as well as by increased functional connectivity of the posterior cingulate cortex with medial temporal lobe regions (Quiroz et al 2015). More recently, we used the WISC-IV, a measure of general intellectual abilities to examine cognitive abilities in these children. We reported in 265 children with the E280A mutation and 1089 non-carriers that they did not differ on any of the WISC-IV indices. Surprisingly, male carriers performed slightly worse than female carriers on working memory (mean difference = -4.97; P = .001) (Fox-Fuller et al., 2021). Some of our ongoing work includes comprehensive examinations of social, educational and developmental histories along with functional brain networks, as markers of synaptic dysfunction in individuals with ADAD, as this is particularly relevant to understanding the impact of PSEN1 mutations on the developing brain and subsequent neurodegenerative changes seen later in life, without the confounds of aging and age-related comorbidities that often exist in late-onset sporadic AD. Disclosures: Financial: Dr. Quiroz receives a consulting fee from Biogen. Non-Financial: Dr. Quiroz is a Hispanic Neuropsychological Society Member-At-Large and serves as the INS Teleneuropsychology Special Interest Group Chair

Objective:Craft story recall test in the National Alzheimer’s Coordinating Center Uniformed Data Set 3 (NACC UDS3) neuropsychological battery has been employed to assess verbal memory and assist clinical diagnosis of mild cognitive impairment (MCI) and dementia. While a Chinese version of the test was adapted, no existing literature has examined the diagnostic validity of the test in Chinese Americans. This study aimed to evaluate the predictive validity of both immediate and delayed recall.Participants and Methods:The Chinese version of Craft Story was administered in to 78 Chinese participants per their language preference of Mandarin or Cantonese. Outcome measures were verbatim and paraphrase recall of the story immediately and after a 20-minute delay. A multiple linear regression was performed to investigate the association of each outcome measure with age, education, gender, age when moved to the U.S., years in the U.S., and testing language. To assess its diagnostic value, cutoff standard deviation scores of -1.5 and -2.0 from the mean of the clinically cognitive normal participants were generated for MCI and dementia diagnoses, respectively. Due to the small sample size, a normative group fitting the mean age (73 years), years of education (12 years), and the majority gender (female) of the current sample were used to identify standard cut points. A receiver-operating characteristic analysis was used to compare predicted diagnosis with actual clinical diagnosis obtained through patients’ overall performance and a consensus meeting by licensed clinicians.Results:Younger age (p < 0.05) and being tested in Mandarin (p < .01) were positively associated with immediate and delayed recall. Strong positive correlations between each measure were observed (all p < .001), indicating a significant relationship between information encoded and retained. Among all the participants, 15 (19.2%) were diagnosed with MCI and 22 (28.2%) with dementia. For MCI diagnosis, the standard cutoff scores demonstrated adequate sensitivity (verbatim=82%, paraphrase=91%) but low specificity (verbatim=44%, paraphrase=67%) in all outcome measures. For dementia diagnosis, delayed recall showed strong sensitivity (100%) and adequate specificity (75%) in both verbatim and paraphrasing scores. Immediate recall paraphrase (sensitivity = 95%, specificity = 50%) showed a better sensitivity but lower specificity than verbatim scoring (sensitivity = 86%, specificity = 58%). The accuracy was higher in delayed recall for both MCI and dementia diagnosis. A preliminary analysis on the optimal cut points indicated higher cutoff scores to distinguish MCI and dementia from clinically cognitive normal population, and from each other (e.g., the optimal cut point for delayed verbatim in distinguishing MCI from normal is 8.0 (sensitivity=89%, specificity=73%, AUC=84.3%)).Conclusions:Consistent with previous literature, Craft Story delayed recall served as a more accurate diagnostic tool for both MCI and dementia compared to immediate recall in older Chinese Americans. However, poor specificity might increase the chance of following false positive subjects in clinical trials. In addition, testing language appeared to impact performance on verbal memory recall of constructed information. Thus, future studies should focus on developing normative scores that address both the overall cultural differences of Chinese Americans and the heterogeneity within this population.

Objective:The Montreal Cognitive Assessment (MOCA) is a brief cognitive screener, widely used by providers to detect mild cognitive impairment (MCI). It encompasses 30 questions, assessing executive functioning, visuospatial skills, language, memory, attention, and orientation. Although the MOCA has been shown to have high sensitivity (90%) and specificity (87%) for detecting MCI, existing studies have primarily included participants who were already diagnosed with amnestic MCI via neuropsychological testing. Since several factors beyond the presence of MCI can contribute to low performance on the MOCA (e.g., premorbid IQ, fatigue, mood symptoms), over-reliance on the MOCA runs the risk of falsely identifying individuals as having cognitive impairment. The MOCA’s memory subtest raises particular concern as there are several language-based tasks between the learning and delay trials, introducing the potential for interference effects. Thus, the MOCA’s ability to accurately identify those at risk for MCI in the community remains unclear. The objective of the present study was to evaluate: (1) the MOCA’s association with neuropsychological memory measures; and (2) its ability to distinguish between neurocognitive groups (intact vs. MCI vs. dementia).Participants and Methods:This study involved a retrospective analysis of fifty-one patients (M age=72.58 [7.90]; M education= 16.37 [16.37]) who underwent neuropsychological evaluation. Standardized scores for total list-learning (HVLT; CVLT-bf) were used to capture memory encoding; retention % scores were used to capture memory storage. MOCA scores included Total MOCA, MOCA-Orientation, and the MOCA Memory Index (MOCA-MEM). MOCA-MEM was calculated based on Julayanont et al., 2014— (Free-Delayed Recall*3) + (Category-Cued Recall*2) + Multiple Choice-Cued Recall. Bivariate correlations were conducted for the MOCA and neuropsychological test scores. Participants were divided into three diagnostic groups, classified by the neuropsychologist: (1) Cognitive Intact (CI; n=13); (2) MCI (n=26); and (3) Major Neurocognitive Disorder/Dementia (MNCD; n=11). Analysis of covariance was used to analyze differences between the cognitive groups on Total MOCA, MOCA-Orientation, and MOCA-MEM.Results:Total MOCA correlated with word-list learning (r=.434, p=.004) and retention% (r=.306, p=.049). MOCA-MEM was correlated with word-list learning (r=.367, p=.042); it did not significantly correlate with retention%. MOCA-Orientation had the strongest correlation with retention0/) (r=.406, p=.009). Means of Total MOCA significantly differed between CI (25.31[2.56]), MCI (22.04[4.14]), and MNCD (15.44[4.13]). MOCA-MEM only differentiated CI (10[3.66]) and MNCD (5.71[2.14]); it did not differentiate MCI (6.94[3.13]) from either CI or MNCD.Conclusions:Our findings suggest that the MOCA has limitations in accurately classifying memory deficits in older adults. First, our study suggests that the MOCA-MEM reflects encoding rather than memory storage. Given that deficiency in encoding may be secondary to other cognitive deficits, such as attention and executive dysfunction, performance on MOCA-MEM cannot readily delineate the presence of an amnestic process. Second, the findings show that MOCA-MEM does not differentiate between patient groups with intact cognition versus MCI, nor those with MCI versus MNCD. These findings argue the importance of neuropsychological evaluation in deciphering patterns of memory performance and the presence of an amnestic process.

Objectives. To study the relationship between measures of immunity and systemic inflammation and structural magnetic resonance imaging (MRI) indicators in patients with pre-dementia cognitive disorders (pre CI) during neurocognitive rehabilitation with the aim of identifying candidate markers for the efficacy of this rehabilitation. Materials and methods. The study group consisted of 49 patients with preMCI with memory impairments; patients were aged 60 years and older and underwent five-week neurorehabilitation courses. The control group consisted of 19 volunteers of similar age without cognitive disorders or immune-inflammatory disorders. Measures of cellular and humoral immunity and inflammatory markers were determined and structural MRI was performed. Results. preMCI was found to be associated with an elevated content of activated natural killers (NK cells) (0.63 ± 0.12% versus 0.22 ± 0.07% in the control group, p = 2.2 10–7). Immunoglobulin G (IgG) levels of <12.5 g/liter in patients with preMCI and scores of <22 on the Montreal Cognitive Assessment (MoCA) were associated with decreases in the volume of the right nucleus accumbens (376 ± 35 mm3 with IgG <12.5 g/liter (p = 0.0013), 429 ± 40 mm3 at IgG >12.5 g/liter, and 480 ± 44 mm3 in the control group), as well as the thickness and volume of some other cortical areas. A logistic regression model (R2 = 0.57; p < 1 10–5; standard error of estimate 2.93) was built, including immunoglobulin G, NK cells, CD8+ NK cell levels, and the volume of the right amygdala, which predicted MoCA scores six months after rehabilitation courses. Conclusions. These studies provide the first demonstration that immune parameters in combination with socio-demographic data and brain morphometric indexes are highly significant as potential prognostic markers reflecting the response to neurorehabilitation.

Background Alzheimer’s disease (AD) exhibits sex differences in pathology and cognitive trajectories. Understanding how these differences manifest across the Alzheimer’s continuum can improve early detection, diagnostics, and interventions. We examined sex differences in the association between cerebrospinal fluid (CSF) pTau181/Aβ42 ratio changes and verbal memory decline across the preclinical and mild cognitive impairment (MCI) stages of AD. Methods In this retrospective, longitudinal, observational study, data were extracted from 401 participants (age range: 55-87.8, 98% non-Hispanic White) of the Alzheimer’s Disease Neuroimaging Initiative cohort study who were classified as either preclinical AD (78 females, 73 males) or MCI (104 females, 146 males) at baseline and had CSF pTau181/Aβ42 ratio and cognitive assessment data at at-least two timepoints. Using regression models, we examined the relationship between changes in CSF pTau181/Aβ42 and verbal memory across all available time points and the moderating role of sex and AD stage over a mean follow-up period of 4 years. Verbal memory was represented by a composite z-score averaging Learning and Delayed Recall z-scores of the Rey Auditory Verbal Learning Test. Covariates included baseline age, education, and apolipoprotein E genotype. Results A significant sex * diagnostic group * biomarker change interaction ( b =-17.47, 95%CI = 27.60 to -7.33, p  = .001) indicated that sex differences in the relationship between changes in CSF pTau181/Aβ42 ratio and verbal memory differed by disease stage. While males in the preclinical AD stage showed steeper memory decline than females with increasing pTau181/Aβ42 ratios, this difference was not statistically significant. In contrast, in the MCI stage, a significant sex * biomarker change interaction ( b  = 10.17, 95% CI = 4.94 to 15.40, p  < .001) indicated that females exhibited significantly steeper memory decline associated with increasing pTau181/Aβ42 ratios compared to males. Conclusion Sex differences in the relationship between AD biomarker levels and cognitive decline vary by disease stage. Although not statistically significant, females demonstrated resilience to memory decline in the preclinical stage, whereas, in the MCI stage, they experienced significantly steeper memory loss compared to males. Results suggest that accounting for sex in biomarker-based methods of disease detection and tracking can improve early detection and intervention in both sexes. Highlights Alzheimer’s disease (AD) biomarkers in cerebrospinal fluid (pTau181/Aβ42) were linked to verbal memory decline differently in women and men, showing that sex modifies biomarker–cognition relationships across disease stages. Despite women showing more resilience to memory decline than men as the AD biomarker advanced in the preclinical stage, this pattern significantly reversed at the MCI stage, whereby. women showed significantly faster memory decline than men as the AD biomarker advanced. Findings suggest a possible “tipping point” in women, where early resilience transitions to greater vulnerability as AD progresses. Results underscore the importance of considering sex when using biomarkers to detect, track, and treat AD. Plain English Summary Alzheimer’s disease (AD) affects men and women differently, but the reasons why remain unclear. Women are more likely to develop AD and often show higher levels of tau, a protein linked to brain changes in the disease. At the same time, women tend to have better memory than men in the very early stages, which may delay diagnosis until the disease has progressed further. In this study, we analyzed data from 401 older adults in the Alzheimer’s Disease Neuroimaging Initiative. Participants were either in the “preclinical” stage of AD (biomarker changes but no memory problems) or had mild cognitive impairment (MCI). We measured changes in spinal fluid proteins (pTau181/Aβ42 ratio) linked to AD and tracked how they related to changes in memory performance over about four years. We found that sex differences depended on the stage of disease. In the preclinical stage, men tended to show faster memory decline than women as AD biomarkers worsened, although this was not statistically significant. In contrast, among people with MCI, women showed significantly faster memory decline than men as biomarkers increased. These findings suggest that women may be more resilient to early Alzheimer’s-related brain changes but reach a “tipping point” at which their memory declines faster once symptoms begin. Considering sex when interpreting AD biomarkers may improve early detection, diagnosis, and treatment for both men and women.

INTRODUCTION Research criteria for prodromal dementia with Lewy bodies (DLB) recently proposed mild cognitive impairment with Lewy bodies (MCI‐LB), delirium‐onset, and psychiatric‐onset presentations. We aimed to classify the DLB prodromal stage in a research cohort against the proposed criteria, and describe the frequency of DLB‐associated clinical features in the prodrome. METHODS Retrospective file review and expert clinician consensus classified DLB participants’ prodromal symptoms against the research criteria and identified clinical features within six domains (cognitive, gait/motor, autonomic, sleep, psychiatric, and sensory). RESULTS Of 45 participants, 80.0% were MCI onset, 11.1% delirium onset, 6.7% psychiatric onset, and 2.2% unclear. All experienced cognitive symptoms. Sleep (80.0%), psychiatric (73.3%), and gait/motor (66.7%) changes were common. The earliest prodromal symptoms were sleep related (35.6%). DISCUSSION MCI‐LB was the most common presentation. Small numbers of delirium‐onset or psychiatric‐onset participants potentially reflects the bias of cohorts recruited from memory assessment services. Improved identification of non‐cognitive DLB prodromes is needed in clinical and research settings. Highlights The mild cognitive impairment prodrome of dementia with Lewy bodies (DLB) was the most common presentation (80% of participants) in this prospective research cohort. Psychiatric‐ and delirium‐onset prodromes were challenging to identify. Multiple non‐cognitive features of DLB were present in the prodrome, in particular, sleep, motor, and psychiatric problems.